scholarly journals Bifidobacterium animalis subsp. lactis A6 Alleviates Obesity Associated with Promoting Mitochondrial Biogenesis and Function of Adipose Tissue in Mice

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1490
Author(s):  
Yanxiong Huo ◽  
Xuhong Lu ◽  
Xiaoyu Wang ◽  
Xifan Wang ◽  
Lingli Chen ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Uncoupling Protein ◽  
Positive Control ◽  
Peroxisome Proliferator ◽  
Adipose Tissues ◽  
Peroxisome Proliferator Activated Receptor ◽  
Bifidobacterium Animalis ◽  
Mitochondrial Biosynthesis ◽  
And Function ◽  
Estrogen Related Receptor

Probiotics are widely known for their health benefits. Mitochondrial dysfunction is related to obesity. The aim of this study was to illuminate whether Bifidobacterium animalis subsp. lactis A6 (BAA6) could improve obesity due to increased mitochondrial biogenesis and function of adipose tissues. Four-week-old male C57BL/6 mice were fed with a high-fat diet (HFD) for 17 weeks. For the final eight weeks, the HFD group was divided into three groups including HFD, HFD with BAA6 (HFD + BAA6 group), and HFD with Akkermansia muciniphila (AKK) (HFD + AKK group as positive control). The composition of the microbiota, serum lipopolysaccharides (LPS), and mitochondrial biosynthesis and function of epididymal adipose tissues were measured. Compared with the HFD group, body weight, relative fat weight, the relative abundance of Oscillibacter and Bilophila, and serum LPS were significantly decreased in the HFD + BAA6 and HFD + AKK groups (p < 0.05). Furthermore, the addition of BAA6 and AKK increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) (by 21.53- and 18.51-fold), estrogen-related receptor α (ERRα) (by 2.83- and 1.24-fold), and uncoupling protein-1 (UCP-1) (by 1.51- and 0.60-fold) in epididymal adipose tissues. Our results suggest that BAA6 could improve obesity associated with promoting mitochondrial biogenesis and function of adipose tissues in mice.

scholarly journals PPAR-gamma induced AKT3 expression increases levels of mitochondrial biogenesis driving prostate cancer

Oncogene ◽  
2021 ◽  
Vol 40 (13) ◽  
pp. 2355-2366
Author(s):  
Laura C. A. Galbraith ◽  
Ernest Mui ◽  
Colin Nixon ◽  
Ann Hedley ◽  
David Strachan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mitochondrial Biogenesis ◽  
Nuclear Export ◽  
Epithelial To Mesenchymal Transition ◽  
Ppar Gamma ◽  
Peroxisome Proliferator ◽  
Serine Threonine Kinase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mesenchymal Transition ◽  
And Function

AbstractPeroxisome Proliferator-Activated Receptor Gamma (PPARG) is one of the three members of the PPAR family of transcription factors. Besides its roles in adipocyte differentiation and lipid metabolism, we recently demonstrated an association between PPARG and metastasis in prostate cancer. In this study a functional effect of PPARG on AKT serine/threonine kinase 3 (AKT3), which ultimately results in a more aggressive disease phenotype was identified. AKT3 has previously been shown to regulate PPARG co-activator 1 alpha (PGC1α) localisation and function through its action on chromosome maintenance region 1 (CRM1). AKT3 promotes PGC1α localisation to the nucleus through its inhibitory effects on CRM1, a known nuclear export protein. Collectively our results demonstrate how PPARG over-expression drives an increase in AKT3 levels, which in turn has the downstream effect of increasing PGC1α localisation within the nucleus, driving mitochondrial biogenesis. Furthermore, this increase in mitochondrial mass provides higher energetic output in the form of elevated ATP levels which may fuel the progression of the tumour cell through epithelial to mesenchymal transition (EMT) and ultimately metastasis.

scholarly journals SIRT1 Activation by Resveratrol Alleviates Cardiac Dysfunction via Mitochondrial Regulation in Diabetic Cardiomyopathy Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Sai Ma ◽  
Jing Feng ◽  
Ran Zhang ◽  
Jiangwei Chen ◽  
Dong Han ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Dynamics ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Beneficial Effects ◽  
Mitochondrial Regulation ◽  
And Function

Background. Diabetic cardiomyopathy (DCM) is a major threat for diabetic patients. Silent information regulator 1 (SIRT1) has a regulatory effect on mitochondrial dynamics, which is associated with DCM pathological changes. Our study aims to investigate whether resveratrol, a SRIT1 activator, could exert a protective effect against DCM. Methods and Results. Cardiac-specific SIRT1 knockout (SIRT1KO) mice were generated using Cre-loxP system. SIRT1KO mice displayed symptoms of DCM, including cardiac hypertrophy and dysfunction, insulin resistance, and abnormal glucose metabolism. DCM and SIRT1KO hearts showed impaired mitochondrial biogenesis and function, while SIRT1 activation by resveratrol reversed this in DCM mice. High glucose caused increased apoptosis, impaired mitochondrial biogenesis, and function in cardiomyocytes, which was alleviated by resveratrol. SIRT1 deletion by both SIRT1KO and shRNA abolished the beneficial effects of resveratrol. Furthermore, the function of SIRT1 is mediated via the deacetylation effect on peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), thus inducing increased expression of nuclear respiratory factor 1 (NRF-1), NRF-2, estrogen-related receptor-α (ERR-α), and mitochondrial transcription factor A (TFAM). Conclusions. Cardiac deletion of SIRT1 caused phenotypes resembling DCM. Activation of SIRT1 by resveratrol ameliorated cardiac injuries in DCM through PGC-1α-mediated mitochondrial regulation. Collectively, SIRT1 may serve as a potential therapeutic target for DCM.

scholarly journals Interferon-Stimulated Gene ISG12b1 Inhibits Adipogenic Differentiation and Mitochondrial Biogenesis in 3T3-L1 Cells

Endocrinology ◽  
2008 ◽  
Vol 150 (3) ◽  
pp. 1217-1224 ◽  
Author(s):  
Bing Li ◽  
Jonghyun Shin ◽  
Kichoon Lee
Keyword(s):  
Mitochondrial Biogenesis ◽  
Adipogenic Differentiation ◽  
Peroxisome Proliferator ◽  
Mitochondrial Transcription ◽  
Peroxisome Proliferator Activated Receptor ◽  
And Function ◽  
Adipocyte Development

Microarray analysis was performed to find a new group of genes or pathways that might be important in adipocyte development and metabolism. Among them, a mouse interferon-stimulated gene 12b1 (ISG12b1) is expressed at a 400-fold higher level in adipocytes compared with stromal-vascular cells. It is predominantly expressed in adipose tissue among other tissues we tested. Developmentally, ISG12b1 mRNA expression was initially inhibited followed by a dramatic induction during both in vivo and in vitro adipogenic differentiation. Adenovirus-mediated overexpression of ISG12b1 inhibited adipogenic differentiation in 3T3-L1 cells as shown by decreased lipid staining with Oil-Red-O and reduction in adipogenic marker proteins including peroxisome proliferator-activated receptor-γ (PPARγ), and CCAAT/enhancer-binding protein-α (C/EBPα). Our bioinformatics analysis for the predicted localization of ISG12b1 protein suggested the mitochondrial localization, which was confirmed by the colocalization of hemagglutinin-tagged ISG12b1 protein with mitochondrial marker MitoTracker. In addition, ISG12b1 protein was exclusively detected in protein extract from the fractionated mitochondria by Western blot analysis. Furthermore, overexpression of ISG12b1 in adipocytes reduced mitochondrial DNA content and gene expression of mitochondrial transcription factor A (mtTFA), nuclear respiratory factor 1 (NRF1), and cytochrome oxidase II, suggesting an inhibitory role of ISG12b1 in mitochondrial biogenesis and function. Activation of mitochondrial biogenesis and function by treatment with PPARγ and PPARα agonists in 3T3-L1 cells and cold exposure in mice induced mitochondrial transcription factors and reduced ISG12 expression. These data demonstrated that mitochondrial-localized ISG12b1 protein inhibits adipocyte differentiation and mitochondrial biogenesis and function, implying the important role of mitochondrial function in adipocyte development and associated diseases. ISG12b1 is predominantly expressed in adipocytes and dramatically induced at the terminal stage of adipogenesis. Functionally, mitochondria-localized ISG12b1 inhibits adipogenic differentiation and mitochondria biogenesis.

Nuclear receptor-mediated regulation of lipid droplet-associated protein gene expression in adipose tissue

2013 ◽  
Vol 14 (3) ◽  
Author(s):  
Mark Christian
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor Α ◽  
Peroxisome Proliferator ◽  
Adipose Tissues ◽  
Peroxisome Proliferator Activated Receptor ◽  
Genes Encoding ◽  
Associated Proteins ◽  
High Throughput Dna Sequencing ◽  
And Function ◽  
White Fat

AbstractIn adipose tissues, nuclear receptors (NRs) have important metabolic actions on cellular lipid-storing capacity through targeted gene regulation. Lipid droplets (LDs) are the organelles for intracellular triacylglycerol (TAG) storage and are present in all eukaryotic cells. They are small in most cells, but in white adipocytes, they can occupy 90% of the cytoplasm. LDs consist of a TAG core surrounded by a phospholipid monolayer and an array of associated proteins that determine size, stability, inter-droplet interaction, and lipid storage capacity. The genes that encode these proteins are more highly expressed in brown compared with white fat, correlating with the greater LD surface area in multilocular brown adipocytes. Gene expression profiling reveals that most NRs are present in adipose tissues, with some showing greater expression in brown compared with white fat, including peroxisome proliferator-activated receptor (PPAR) α, estrogen-related receptor α, and NURR1. NR signaling is important for the regulated expression of most genes that encode LD-associated proteins. For example, estradiol signals via estrogen receptor α to regulate the levels of PLIN1 and the lipase ATGL controlling LD size and total lipid accumulation. PPARγ is essential for adipocyte differentiation and function, and analysis of data obtained through chromatin immunoprecipitation followed by high-throughput DNA sequencing shows that it binds to the promoters of many genes encoding LD proteins in adipocytes. Of these genes, the greatest PPARγ binding was to regulatory regions for

scholarly journals Repeated Oral Administration of Flavan-3-ols Induces Browning in Mice Adipose Tissues Through Sympathetic Nerve Activation

2021 ◽  
Author(s):  
Yuko Ishii ◽  
Orie Muta ◽  
Tomohiro Teshima ◽  
Nayuta Hirasima ◽  
Minayu Odaka ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Transmembrane Protein ◽  
Repeated Administration ◽  
Peroxisome Proliferator ◽  
Adipose Tissues ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brown Adipose ◽  
Sympathetic Nerve Activation ◽  
Pr Domain ◽  
The Impact

We previously found increases in uncoupling protein (Ucp)-1 transcription in brown adipose tissue (BAT) of mice following a single oral dose of flavan 3-ols (FL), a fraction of catechins and procyanidins. It was confirmed that these changes were totally reduced by co-treatment of adrenaline blockers. According to these previous results, FL possibly activates sympathetic nervous system (SNS). In this study, we confirmed the marked increase in urinary catecholamine (CA) s projecting SNS activity following a single dose of 50 mg/kg FL. In addition, we examined the impact of the repeated administration of 50 mg/kg FL for 14 days on adipose tissues in mice. In BAT, FL tended to increase the level of Ucp-1 along with thermogenic transcriptome factors, such as peroxisome proliferator-activated receptor &gamma; coactivator (PGC)-1&alpha; and PR domain-containing (PRDM)1. Transcription of browning markers, such as CD137 and transmembrane protein (TMEM) 26 in addition to PGC-1&alpha; were increased in epididymal adipose (eWAT) by FL. A multilocular morphology with cell size reduction was shown in the inguinal adipose (iWAT), together with increasing the level of Ucp-1 following administration of FL. These results suggest that FL produces browning in adipose through activation of the SNS.

scholarly journals Repeated Oral Administration of Flavan-3-ols Induces Browning in Mice Adipose Tissues through Sympathetic Nerve Activation

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4214
Author(s):  
Yuko Ishii ◽  
Orie Muta ◽  
Tomohiro Teshima ◽  
Nayuta Hirasima ◽  
Minayu Odaka ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Transmembrane Protein ◽  
Repeated Administration ◽  
Peroxisome Proliferator ◽  
Adipose Tissues ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brown Adipose ◽  
Sympathetic Nerve Activation ◽  
Pr Domain ◽  
The Impact

We previously found increases in uncoupling protein (Ucp)-1 transcription in brown adipose tissue (BAT) of mice following a single oral dose of flavan 3-ol (FL)s, a fraction of catechins and procyanidins. It was confirmed that these changes were totally reduced by co-treatment of adrenaline blockers. According to these previous results, FLs possibly activate sympathetic nervous system (SNS). In this study, we confirmed the marked increase in urinary catecholamine (CA) s projecting SNS activity following a single dose of 50 mg/kg FLs. In addition, we examined the impact of the repeated administration of 50 mg/kg FLs for 14 days on adipose tissues in mice. In BAT, FLs tended to increase the level of Ucp-1 along with significant increase of thermogenic transcriptome factors expressions, such as peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and PR domain-containing (PRDM)1. Expression of browning markers, CD137 and transmembrane protein (TMEM) 26, in addition to PGC-1α were increased in epididymal adipose (eWAT) by FLs. A multilocular morphology with cell size reduction was shown in the inguinal adipose (iWAT), together with increasing the level of Ucp-1 by FLs. These results exert that FLs induce browning in adipose, and this change is possibly produced by the activation of the SNS.

scholarly journals Empagliflozin Induces White Adipocyte Browning and Modulates Mitochondrial Dynamics in KK Cg-Ay/J Mice and Mouse Adipocytes

2021 ◽  
Vol 12 ◽  
Author(s):  
Linxin Xu ◽  
Chaofei Xu ◽  
Xiangyang Liu ◽  
Xiaoyu Li ◽  
Ting Li ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Dynamics ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Compound C ◽  
Kkay Mice ◽  
Brown Adipose ◽  
And Function

Background: White adipose tissue (WAT) browning is a promising target for obesity prevention and treatment. Empagliflozin has emerged as an agent with weight-loss potential in clinical and in vivo studies, but the mechanisms underlying its effect are not fully understood. Here, we investigated whether empagliflozin could induce WAT browning and mitochondrial alterations in KK Cg-Ay/J (KKAy) mice, and explored the mechanisms of its effects.Methods: Eight-week-old male KKAy mice were administered empagliflozin or saline for 8 weeks and compared with control C57BL/6J mice. Mature 3T3-L1 adipocytes were treated in the presence or absence of empagliflozin. Mitochondrial biosynthesis, dynamics, and function were evaluated by gene expression analyses, fluorescence microscopy, and enzymatic assays. The roles of adenosine monophosphate–activated protein kinase (AMPK) and peroxisome proliferator–activated receptor-γ coactivator-1-alpha (PGC-1α) were determined through AICAR (5-Aminoimidazole-4-carboxamide1-β-D-ribofuranoside)/Compound C and RNA interference, respectively.Results: Empagliflozin substantially reduced the bodyweight of KKAy mice. Mice treated with empagliflozin exhibited elevated cold-induced thermogenesis and higher expression levels of uncoupling protein 1 (UCP1) and other brown adipose tissue signature proteins in epididymal and perirenal WAT, which was an indication of browning in these WAT depots. At the same time, empagliflozin enhanced fusion protein mitofusin 2 (MFN2) expression, while decreasing the levels of the fission marker phosphorylated dynamin-related protein 1 (Ser616) [p-DRP1 (Ser616)] in epididymal and perirenal WAT. Empagliflozin also increased mitochondrial biogenesis and fusion, improved mitochondrial integrity and function, and promoted browning of 3T3-L1 adipocytes. Further, we found that AMPK signaling activity played an indispensable role in empagliflozin-induced browning and mitochondrial biogenesis, and that PGC-1α was required for empagliflozin-induced fusion. Whether empagliflozin activates AMPK by inhibition of SGLT2 or by independent mechanisms remains to be tested.Conclusion: Our results suggest that empagliflozin is a promising anti-obesity treatment, which can immediately induce WAT browning mitochondrial biogenesis, and regulate mitochondrial dynamics.

Triiodothyronine induces UCP-1 expression and mitochondrial biogenesis in human adipocytes

2012 ◽  
Vol 302 (2) ◽  
pp. C463-C472 ◽  
Author(s):  
Joo-Young Lee ◽  
Nobuyuki Takahashi ◽  
Midori Yasubuchi ◽  
Young-Il Kim ◽  
Hikari Hashizaki ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Mitochondrial Biogenesis ◽  
Uncoupling Protein ◽  
Human Adipose Tissue ◽  
Energy Utilization ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brown Adipose

Uncoupling protein (UCP)-1 expressed in brown adipose tissue plays an important role in thermogenesis. Recent data suggest that brown-like adipocytes in white adipose tissue (WAT) and skeletal muscle play a crucial role in the regulation of body weight. Understanding of the mechanism underlying the increase in UCP-1 expression level in these organs should, therefore, provide an approach to managing obesity. The thyroid hormone (TH) has profound effects on mitochondrial biogenesis and promotes the mRNA expression of UCP in skeletal muscle and brown adipose tissue. However, the action of TH on the induction of brown-like adipocytes in WAT has not been elucidated. Thus we investigate whether TH could regulate UCP-1 expression in WAT using multipotent cells isolated from human adipose tissue. In this study, triiodothyronine (T3) treatment induced UCP-1 expression and mitochondrial biogenesis, accompanied by the induction of the CCAAT/enhancer binding protein, peroxisome proliferator-activated receptor-γ coactivator-1α, and nuclear respiratory factor-1 in differentiated human multipotent adipose-derived stem cells. The effects of T3 on UCP-1 induction were dependent on TH receptor-β. Moreover, T3 treatment increased oxygen consumption rate. These findings indicate that T3 is an active modulator, which induces energy utilization in white adipocytes through the regulation of UCP-1 expression and mitochondrial biogenesis. Our findings provide evidence that T3 serves as a bipotential mediator of mitochondrial biogenesis.

scholarly journals Receptor Interacting Protein 140 Regulates Expression of Uncoupling Protein 1 in Adipocytes through Specific Peroxisome Proliferator Activated Receptor Isoforms and Estrogen-Related Receptor α

2007 ◽  
Vol 21 (7) ◽  
pp. 1581-1592 ◽  
Author(s):  
Darja Debevec ◽  
Mark Christian ◽  
Daniel Morganstein ◽  
Asha Seth ◽  
Birger Herzog ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Uncoupling Protein 1 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Interacting Protein ◽  
White Adipocytes ◽  
Receptor Isoforms ◽  
Ucp1 Expression ◽  
Peroxisome Proliferator Activated Receptors ◽  
Estrogen Related Receptor

Abstract Expression of uncoupling protein 1 (Ucp1) mRNA is elevated in differentiated adipocytes derived from brown or white adipose tissue devoid of the nuclear receptor corepressor receptor interacting protein 140 (RIP140). Increased expression is mediated in part by the recruitment of peroxisome proliferator activated receptors α and γ, together with estrogen-related receptor α, which functions through a novel binding site on the Ucp1 enhancer. This demonstrates that regulation of Ucp1 expression in the absence of RIP140 involves derepression of at least three different nuclear receptors. The ability to increase expression of Ucp1 by β-adrenergic signaling is independent of RIP140, as shown by the action of the β3-adrenergic agonist CL 316,243 to stimulate expression in both brown and white adipocytes in the presence and absence of the corepressor. Therefore, the expression of this metabolic uncoupling protein in adipose cells is regulated by inhibition as well as activation of distinct signaling pathways.

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